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Effect of MisMatch repair deficiency on metastasis occurrence in a syngeneic mouse model
Laplante, P. Rosa, R. Nebot-Bral, L. Goulas, J. Pouvelle, C. Nikolaev, S. Silvin, A. Kannouche, P. L.
Laplante, P.
Rosa, R.
Nebot-Bral, L.
Goulas, J.
Pouvelle, C.
Nikolaev, S.
Silvin, A.
Kannouche, P. L.
Abstract
Mismatch repair deficiency leads to high mutation rates and microsatellite instability (MSI-H), associated with immune infiltration and responsiveness to immunotherapies. In early stages, MSI-H tumors generally have a better prognosis and lower metastatic potential than microsatellite-stable (MSS) tumors, especially in colorectal cancer. However, in advanced stages, MSI-H tumors lose this survival advantage for reasons that remain unclear. We developed a syngeneic mouse model of MSI cancer by knocking out the MMR gene Msh2 in the metastatic 4T1 breast cancer cell line. This model mirrored genomic features of MSI-H cancers and showed reduction in metastatic incidence compared to their MSS counterparts. In MSI-H tumors, we observed an enrichment of immune gene-signatures that negatively correlated with metastasis incidence. A hybrid epithelial-mesenchymal signature, related to aggressiveness was detected only in metastatic MSI-H tumors. Interestingly, we identified immature myeloid cells at primary and metastatic sites in MSI-H tumor-bearing mice, suggesting that MMR deficiency elicits specific immune responses beyond T-cell activation.
Description
Date
2025
Publisher
Collections
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Article
Citation
Laplante P, Rosa R, Nebot-Bral L, Goulas J, Pouvelle C, Nikolaev S, et al. Effect of MisMatch repair deficiency on metastasis occurrence in a syngeneic mouse model. NEOPLASIA. 2025 APR;62. PubMed PMID: WOS:001431998800001. English.